Changes in blood flow to the intestine occur in both normal and pathological states (e.g., digestion, exercise, shock, cholera, etc.), and intestinal blood flow has been studied in these states. Yet, the paramount function of the circulation--that of delivering oxygen to the tissue--has not been studied systematically in the intestine. Furthermore, because there is increasing evidence that gut ischemia plays a role in a broad spectrum of diseases, it is imperative that we understand the mechanisms regulating the delivery of oxygen to intestinal tissues. In acute conditions, two means are available for regulating the delivery of oxygen to tissues: (1) changes in blood flow produced by changing vascular resistance, and (2) changes in the diffusion parameters (capillary surface area and diffusion distance) which are caused by opening or closing precapillary sphincters to regulate the density of the perfused capillary bed. We have previously shown both in computer models of the intestinal circulation and in animal experiments that changes in capillary density may be more important in controlling oxygen delivery than the changes in blood flow which normally occur. In the proposed investigation, we will study the effects of various neurohumoral and pharmacological agents on intestinal oxygen uptake; and by measuring Rb extraction or capillary filtration coefficients as indices of capillary density, we will determine the mechanism through which the agents affect intestinal oxygen uptake. By using the computer as a tool to integrate the complex interrelationships among the parameters governing the intestinal microcirculation, and by updating the model with the data obtained in animal experiments, we hope to gain further insight into the mechanisms regulating the delivery of oxygen to intestinal tissues. BIBLIOGRAPHIC REFERENCES: Shepherd, A. P., W. Pawlik, D. Mailman, T. F. Burks and E. D. Jacobson, Effects of Vasoconstrictors on intestinal vascular resistance and oxygen extraction. Amer. J. Physiol. 230:298-305, 1976.